Publications by authors named "Mark Mulligan"

Background: Following maternal COVID-19 vaccination, the persistence of antibodies in sera and breast milk for mothers and infants is not well characterized. We sought to describe the persistence of antibodies through 2 months after delivery in maternal and infant serum and breast milk following maternal COVID-19 mRNA vaccination and to examine differences by receipt of booster dose during pregnancy or postpartum.

Methods: This is a prospective cohort study with enrollment from July 2021 to January 2022 at 9 US academic sites.

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We performed a systems vaccinology analysis to investigate immune responses in humans to an H5N1 influenza vaccine, with and without the AS03 adjuvant, to identify factors influencing antibody response magnitude and durability. Our findings revealed a platelet and adhesion-related blood transcriptional signature on day 7 that predicted the longevity of the antibody response, suggesting a potential role for platelets in modulating antibody response durability. As platelets originate from megakaryocytes, we explored the effect of thrombopoietin (TPO)-mediated megakaryocyte activation on antibody response longevity.

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  • Rabies remains a high-mortality disease, prompting the exploration of a novel vaccine called ChAd155-RG, which uses a genetically modified chimpanzee adenovirus vector to improve immunization logistics.
  • A phase 1 clinical trial involving healthy adults compared the safety and immune response of ChAd155-RG to the standard vaccine, RabAvert, assessing factors like side effects and antibody levels.
  • Results showed that while ChAd155-RG was generally safe, it demonstrated lower and less lasting antibody responses against rabies compared to RabAvert, possibly influenced by participants' preexisting immunity to the adenovirus vector used in the vaccine.
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There are millions of river barriers worldwide, ranging from wooden locks to concrete dams, many of which form associated impoundments to store water in small ponds or large reservoirs. Besides their benefits, there is growing recognition of important environmental and social trade-offs related to these artificial structures. However, global datasets describing their characteristics and geographical distribution are often biased towards particular regions or specific applications, such as hydropower dams affecting fish migration, and are thus not globally consistent.

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  • rVSVΔG-ZEBOV-GP is a vaccine that helps protect people from the Ebola virus and is the first one to be officially approved for this purpose.
  • This study wanted to see how well a booster shot given 18 months after the first vaccine dose helped keep the immune response strong for a longer time.
  • Healthy adults who might be at risk of exposure to Ebola participated in the trial, and the results measured their antibody levels 36 months after the first vaccination to compare those who got the booster with those who did not.
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The recent pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) highlighted a critical need to discover more effective antivirals. While therapeutics for SARS-CoV-2 exist, its nonstructural protein 13 (Nsp13) remains a clinically untapped target. Nsp13 is a helicase responsible for unwinding double-stranded RNA during viral replication and is essential for propagation.

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Memory CD4 T cells are critical to human immunity, yet it is unclear whether viral inflammation during memory formation has long-term consequences. Here, we compared transcriptional and epigenetic landscapes of Spike (S)-specific memory CD4 T cells in 24 individuals whose first exposure to S was via SARS-CoV-2 infection or mRNA vaccination. Nearly 2 years after memory formation, S-specific CD4 T cells established by infection remained enriched for transcripts related to cytotoxicity and for interferon-stimulated genes, likely because of a chromatin accessibility landscape altered by inflammation.

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  • The Omicron XBB.1.5 variant of SARS-CoV-2 was first identified in New York City and quickly became the dominant strain by early 2023.
  • Due to the rise in variants like XBB.1.5, Pfizer-BioNTech and Moderna updated their COVID-19 mRNA vaccines in September 2023, adding a specific component for this variant.
  • A phylogeographic study showed XBB.1.5 likely originated in or near NYC, spreading at a rate similar to the Alpha variant, and there was no significant difference in the prevalence of XBB.1.5 between boosted and unvaccinated individuals in genomic analyses.
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Objectives: (1) To plot the trajectory of humoral and cellular immune responses to the primary (two-dose) COVID-19 mRNA series and the third/booster dose in B-cell-depleted multiple sclerosis (MS) patients up to 2 years post-vaccination; (2) to identify predictors of immune responses to vaccination; and (3) to assess the impact of intercurrent COVID-19 infections on SARS CoV-2-specific immunity.

Methods: Sixty ocrelizumab-treated MS patients were enrolled from NYU (New York) and University of Colorado (Anschutz) MS Centers. Samples were collected pre-vaccination, and then 4, 12, 24, and 48 weeks post-primary series, and 4, 12, 24, and 48 weeks post-booster.

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  • The Upper White Nile basin is vital for the livelihoods and ecosystems of millions in East Africa, but faces severe environmental pressures from population growth, urbanization, and climate change.
  • Existing frameworks for managing water, energy, and food resources often overlook local perspectives, making them less practical for real-world application.
  • The study emphasizes the need to develop indicators that consider local stakeholder concerns, particularly regarding water quality and ecosystem health, to better address sustainability challenges in the basin.
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The head domain of the hemagglutinin of influenza viruses plays a dominant role in the antibody response due to the presence of immunodominant antigenic sites that are the main targets of host neutralizing antibodies. For the H1 hemagglutinin, five major antigenic sites defined as Sa, Sb, Ca1, Ca2, and Cb have been described. Although previous studies have focused on defining the hierarchy of the antigenic sites of the hemagglutinin in different human cohorts, it is still unclear if the immunodominance profile of the antigenic sites might change with the antibody levels of individuals or if other demographic factors (such as exposure history, sex, or age) could also influence the importance of the antigenic sites.

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Ebola virus disease (EVD) is a filoviral infection caused by virus species of the Ebolavirus genus including Zaire ebolavirus (EBOV) and Sudan ebolavirus (SUDV). We investigated the safety and immunogenicity of a heterologous prime-boost regimen involving a chimpanzee adenovirus 3 vectored Ebola vaccine [either monovalent (cAd3-EBOZ) or bivalent (cAd3-EBO)] prime followed by a recombinant modified vaccinia virus Ankara EBOV vaccine (MVA-EbolaZ) boost in two phase 1/1b randomized open-label clinical trials in healthy adults in the United States (US) and Uganda (UG). Trial US (NCT02408913) enrolled 140 participants, including 26 EVD vaccine-naïve and 114 cAd3-Ebola-experienced participants (April-November 2015).

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Introduction: A surge of human influenza A(H7N9) cases began in 2016 in China from an antigenically distinct lineage. Data are needed about the safety and immunogenicity of 2013 and 2017 A(H7N9) inactivated influenza vaccines (IIVs) and the effects of AS03 adjuvant, prime-boost interval, and priming effects of 2013 and 2017 A(H7N9) IIVs.

Methods: Healthy adults (n = 180), ages 19-50 years, were enrolled into this partially blinded, randomized, multicenter phase 2 clinical trial.

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  • Maternal vaccination with mRNA COVID-19 vaccines can help protect infants from COVID-19 by passing antibodies through the placenta during pregnancy.
  • Infants born to mothers who received a booster shot had higher levels of protective antibodies and were 56% less likely to contract COVID-19 in their first 6 months compared to those whose mothers did not receive a booster.
  • The study suggests that higher antibody levels at delivery reduce infection risk significantly, emphasizing the importance of maternal vaccination until infants can be vaccinated themselves.
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SARS-CoV-2 infection and vaccination elicit potent immune responses. Our study presents a comprehensive multimodal single-cell analysis of blood from COVID-19 patients and healthy volunteers receiving the SARS-CoV-2 vaccine and booster. We profiled immune responses via transcriptional analysis and lymphocyte repertoire reconstruction.

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Meeting global commitments to conservation, climate, and sustainable development requires consideration of synergies and tradeoffs among targets. We evaluate the spatial congruence of ecosystems providing globally high levels of nature's contributions to people, biodiversity, and areas with high development potential across several sectors. We find that conserving approximately half of global land area through protection or sustainable management could provide 90% of the current levels of ten of nature's contributions to people and meet minimum representation targets for 26,709 terrestrial vertebrate species.

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Background: Human infections with the avian influenza A(H7N9) virus were first reported in China in 2013 and continued to occur in annual waves. In the 2016/2017 fifth wave, Yangtze River Delta (YRD) lineage viruses, which differed antigenically from those of earlier waves, predominated.

Methods: In this phase 2 double-blinded trial we randomized 720 adults ≥ 19 years of age to receive two injections of a YRD lineage inactivated A/Hong Kong/125/2017 fifth-wave H7N9 vaccine, given 21 days apart, at doses of 3.

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Background: A controlled human infection model for assessing tuberculosis (TB) immunity can accelerate new vaccine development.

Methods: In this phase 1 dose escalation trial, 92 healthy adults received a single intradermal injection of 2 × 106 to 16 × 106 colony-forming units of Bacillus Calmette-Guérin (BCG). The primary endpoints were safety and BCG shedding as measured by quantitative polymerase chain reaction, colony-forming unit plating, and MGIT BACTEC culture.

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  • The Zika virus has caused autochthonous transmission in 87 countries since 2015, posing risks like Guillain-Barré syndrome and complications in pregnancy, underscoring an urgent need for effective vaccines and enhanced understanding of immunity against ZIKV.
  • Researchers developed a new diagnostic test called blockade-of-binding (BOB) ELISA, using specific monoclonal antibodies to differentiate ZIKV from other flaviviruses, and found it performed better than traditional tests in validating ZIKV infections and assessing vaccine responses.
  • The BOB assays demonstrated high sensitivity and specificity in detecting antibodies from recent and past ZIKV infections, indicating potential for broader applications in monitoring ZIKV immunity and evaluating vaccine efficacy.
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Background: High rates of vaccination and natural infection drive immunity and redirect selective viral adaptation. Updated boosters are installed to cope with drifted viruses, yet data on adaptive evolution under increasing immune pressure in a real-world situation are lacking.

Methods: Cross-sectional study to characterise SARS-CoV-2 mutational dynamics and selective adaptation over >1 year in relation to vaccine status, viral phylogenetics, and associated clinical and demographic variables.

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One of the main challenges in the fight against coronavirus disease 2019 (COVID-19) stems from the ongoing evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into multiple variants. To address this hurdle, research groups around the world have independently developed protocols to isolate these variants from clinical samples. These isolates are then used in translational and basic research-for example, in vaccine development, drug screening or characterizing SARS-CoV-2 biology and pathogenesis.

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Background: Noroviruses (NoVs) are a leading cause of non-bacterial gastroenteritis in young children and adults worldwide. Snow Mountain Virus (SMV) is the prototype of NoV GII genotype 2 (GII.2) that has been developed as a viral model for human challenge models, an important tool for studying pathogenesis and immune response of NoV infections and for evaluating NoV vaccine candidates.

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The immune response to SARS-CoV-2 antigen after infection or vaccination is defined by the durable production of antibodies and T cells. Population-based monitoring typically focuses on antibody titer, but there is a need for improved characterization and quantification of T cell responses. Here, we used multimodal sequencing technologies to perform a longitudinal analysis of circulating human leukocytes collected before and after immunization with the mRNA vaccine BNT162b2.

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